MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.
In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.
The technology has been licensed to Tome Biosciences — a biotech co-founded by the duo back in February of 2021 and backed by ARCH, Google’s venture arm, a16z, Longwood Fund, Polaris Partners and Alexandria Venture, which joined after its Series A, according to a recent pitch deck obtained by Endpoints News.
Sana Biotechnology also has a stake in the company, according to an April SEC filing.
Abudayyeh and Gootenberg declined to comment on Tome. The Watertown, MA-based biotech is led by CEO Rahul Kakkar and has more than 80 full-time employees as of the third quarter of this year, according to the pitch deck slides.
In the paper, the researchers explain how they fuse two existing technologies: a prime editor, which the Broad’s David Liu pioneered and spun out into the startup Prime Medicine, and an integrase, an enzyme some viruses use to infect bacteria by inserting their DNA into the host cells.
The idea behind the combined technologies is that integrases on their own aren’t easily engineered to insert at any location besides their specific target sequence, but they’re capable of carrying big sequences. Prime editors, meanwhile, can be engineered to target and edit specific spots, but only in short bits — just enough to stick in a target sequence for the integrase. By combining the two in PASTE, researchers can insert sequences as large as 36,000 base pairs, in the spots that they want.
Abudayyeh told Endpoints News that unlike current gene-editing approaches, which can only go after single mutations of a disease at once, PASTE could address many mutations at the same time at once by replacing the whole gene. In addition, the technique doesn’t create a double-stranded break in the DNA, reducing the risk of unwanted insertions or deletions, he said.
In a paper published last December in Nature Biotechnology, Liu’s lab described a similar approach. The only difference is that Liu’s lab opted not to fuse all the machinery together, having the prime editor and integrase work separately. In their paper, Gootenberg and Abudayyeh report higher efficiency than Liu’s paper did. (A month before the Liu lab’s work was published in Nature Biotechnology, both teams had released pre-prints of their work within a day of each other.)
Liu said in an email, “In our lab’s hands the prime editor–recombinase fusion does not on average work better than simply expressing the recombinase as a separate protein, and in some cases, the fusions worked less efficiently than the separately expressed proteins.”
Both Kiran Musunuru, University of Pennsylvania professor and Verve Therapeutics co-founder, and Sam Sternberg, Columbia professor and Prime advisor, said that they thought both were similar. “Is there a big difference? Probably not in the grand scheme of things,” Musunuru said. “I don’t think it matters too much whether it’s two different proteins made separately or whether it’s a single protein. They both seem to work reasonably well.”
Musunuru, who researches the genetics of heart disease, said he’s been using PASTE in his own lab too, after the preprint was published last year, though while his lab has gotten the technology to work in cells, it hasn’t gotten it to work in mice. Verve uses a form of gene editing called base editing, licensed from Liu’s other biotech Beam Therapeutics.
Notably, Tome doesn’t have a license with Prime Medicine, which houses Liu’s prime editing patents from the Broad, and is not in talks for one, a spokesperson for Prime Medicine told Endpoints.
Abudayyeh and Gootenberg emphasized that while they used prime editing in their paper, the more general PASTE framework was not limited to prime editing. “Prime is one example, but not the only way to do it,” Gootenberg said.
Musunuru wasn’t so sure, noting that he didn’t see how you could make the technique programmable, or targetable, “without something very similar to prime editing.”
Abudayyeh and Gootenberg are alumni of CRISPR pioneer Feng Zhang’s lab. They’ve launched several biotechs, including Sherlock Biosciences and Proof Diagnostics, both diagnostics companies they co-founded with Zhang and others, and Moment Biosciences, a stealth company that is developing “precision microbiome therapy,” according to a Massachusetts corporate filing. And then, of course, there’s Tome.
The industry is paying a lot of attention and money to the next iterations of CRISPR. Prime launched last year with $315 million and raised $175 million when it went public in October. Then there’s Tessera, which in August raised $300 million, putting its total funds raised over the $500 million mark. In February, Intellia, which is using CRISPR to edit genes directly in the body, bought for $45 million cash little-known Rewrite Therapeutics, which its investor called “kind of CRISPR 2.0,” a moniker applied to the likes of base and prime editing, though little else was said of its technology.
Researchers are still in the early days of turning such a technology into a commercial therapy — prime editing has never been used in humans. In Abudayyeh and Gootenberg’s paper, they were able to get the DNA they wanted into a mouse’s liver cells less than 3% of the time. Musunuru said that there was a lot of space for improvement, noting that they would have to get to around at least 10% to have some therapeutic effect.
In the pitch deck, Tome says it hopes to be in the clinic by 2026.
Editors note: This story was corrected to remove a reference to the timeline of research by Liu’s team, and a line was added to clarify the timing of when preprints from each team were published.
The Asia Pacific region, which has more than 6,772 trial sites each with access to an average of 2,136 million people, has considerable underutilized capacity presenting an opportunity for growth in multinational trials in the region.
Demand for Asia Pacific trial sites is strong with almost half of the more than 27,000 clinical trials initiated in 2021 having in Asia Pacific, according to the latest analysis from GlobalData in a new report titled State of the Global Biotech Landscape: Where the Opportunities Lie.
Drug pricing watchdog ICER said that the uncertainty in the health benefits of two potential Alzheimer’s drugs makes it challenging to assess their future cost-effectiveness, according to a draft report released Thursday morning.
The report evaluates Biogen and Eisai’s lecanemab and Eli Lilly’s donanemab, both of which are amyloid-clearing antibody drugs due for FDA decisions in the coming weeks and months. The FDA’s deadline for a decision on lecanemab’s accelerated approval is Jan. 6, while the deadline for donanemab is estimated to be in February.
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Just ahead of what would have been his second anniversary as chief financial officer at MorphoSys, Sung Lee put out word that he is exiting the German biotech and headed back to the US.
The biotech says that Lee will be returning to California — for personal reasons.
Lee’s tenure at MorphoSys has been eventful. He’s been given credit for playing a major role in the Constellation buyout just months after his arrival, which delivered pelabresib (CPI-0610), billed at the time as a potential first and best-in-class BET inhibitor, and CPI-0209, a second-generation EZH2 inhibitor.
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Vaxcyte will pay Sutro Biopharma as much as $157.5 million to take over the manufacturing and future development of the cell-free extract used for its vaccine candidates.
Under the agreement, Vaxcyte is paying $22.5 million upfront for the option to work with a contract manufacturer to make the cell-free extract and to develop it further. If it exercises the option, it will pay $75 million, plus as much as $60 million in additional milestone payments.
Two psychiatric-based drug development companies, Vistagen and Pherin Pharmaceuticals, are merging in a deal worth 12.4 million shares and a “nominal amount” of cash, Vistagen announced Wednesday.
According to SEC filings, Vistagen has estimated that the amount of cash will be under $50,000. Vistagen has also agreed to pay Pherin’s merger-related fees up to $325,000.
By acquiring Pherin, Vistagen will take over the company’s existing drug pipeline, including two advanced products and three in the early clinical stage. Vistagen focuses on disorders like anxiety and depression, while Pherin develops neuroactive steroids, known as pherine compounds, for neuropsychiatric and neuroendocrine conditions.
Despite a year littered with setbacks, ProQR Therapeutics is closing 2022 on a high note.
The Dutch biotech is expanding its RNA editing collaboration with Eli Lilly, with a potentially large payoff down the line, the companies announced early Thursday morning.
Lilly is putting down $75 million in upfront cash and equity, with a $50 million option to expand the deal further in the future. There’s also now $3.75 billion in biobucks on the table, compared with $1.25 billion when the pair signed their original deal in September 2021.
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While all has gone quiet on the M&A rumor front for Seagen, one of the pioneers in antibody-drug conjugates, Merck has been racking up deal after deal for ADCs out of a Chengdu, China-based partner.
In the latest of three tie-ups with Kelun-Biotech, Merck is likely entering the history books with a deal that could balloon to $9.3 billion in back-end payments — that’s if seven ADCs make it to market. That’s a huge if, as drug R&D is notorious for an approximately 10% success rate, but the immediate boost to Kelun’s coffers is not small: $175 million plus an intended equity investment of undisclosed size.
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Biology tools company Berkeley Lights will acquire IsoPlexis in a $57.8 million all-stock transaction agreement announced Wednesday. The new company will be named PhenomeX, with Berkeley Lights shareholders owning about 75% and IsoPlexis holders the rest.
Berkeley Lights CEO Siddhartha Kadia will be the CEO of the new company and a member of the board of directors. IsoPlexis CEO Sean Mackay will stay on as chief product officer of PhenomeX.
Enveda Biosciences will enter the clinic next year with at least one of its three main programs thanks to a $68 million boost in financing — about $55 million via equity and the remainder debt.
Founded by an early employee at AI startup Recursion Pharmaceuticals, Enveda has adjusted its priorities since disclosing a $51 million Series A in June 2021. At the time, CEO Viswa Colluru told Endpoints News the three core areas were Wilson disease, NASH and Parkinson’s.
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